Selected peptides targeted to the NMDA receptor channel protect neurons from excitotoxic death

Nature Biotechnology volume 16, pages286–291(1998)Cite this article

Abstract

Excitotoxic neuronal death, associated with neurodegeneration and stroke, is triggered primarily by massive Ca2+ influx arising from overactivation of glutamate receptor channels of the N-methyl-D-aspartate (NMDA) subtype. To search for channel blockers, synthetic combinatorial libraries were assayed for block of agonist-evoked currents by the human NR1-NR2A NMDA receptor subunits expressed in amphibian oocytes. A set of arginine-rich hexapeptides selectively blocked the NMDA receptor channel with IC50, approximately 100 nM, a potency similar to clinically tolerated blockers such as memantine, and only marginally blocked on non-NMDA glutamate receptors. These peptides prevent neuronal cell death elicited by an excitotoxic insult on hippocampal cultures.

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Author notes

  1. Enrique Perez-Paya

    Present address: Departament of Biochemistry and Molecular Biology, University of Valencia, 46100, Burjassot, Valencia, Spain

  2. Antonio V. Ferrer-Montiel and Jaime M. Merino: These authors contributed equally to this work.

Affiliations

  1. Department of Biology, University of California, San Diego, La Jolla, CA, 92093-0366

    Antonio V. Ferrer-Montiel, Jaime M. Merino & Mauricio Montal

  2. Torrey Pines Institute for Molecular Studies, San Diego, CA, 92121

    Sylvie E. Blondelle, Enrique Perez-Paya & Richard A. Houghten

Authors
  1. Antonio V. Ferrer-Montiel
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  4. Enrique Perez-Paya
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  6. Mauricio Montal
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Correspondence to Mauricio Montal.

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Ferrer-Montiel, A., Merino, J., Blondelle, S. et al. Selected peptides targeted to the NMDA receptor channel protect neurons from excitotoxic death. Nat Biotechnol 16, 286–291 (1998). https://doi.org/10.1038/nbt0398-286

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